Sustained Histologic Response Is Common In The Absence Of Virologic Response To Interferon (Ifn) Therapy For Chronic Hepatitis C (Hcv)

C3H SCID mice pre-treated with 250R total body g-radiation were reconstituted with 3-5x107 allogeneic bone marrow (male: BALB/c[H-2Kd]) by intravenous injection.Four weeks post-reconstitution, liver NPC cells were isolated by pronase digestion followed by differential centrifugation and NPC engraftment was assayed by FACS analysis.The NPC fraction demonstrated a large population (-40%) of donor-origin H-2K b cells.Extra-hepatic reconstitution of the SCID mouse was verified by CD3 +, CD4 + and CD8 ÷ staining of peripheral blood, thymus, and spleen which were entirely of H-2K a background (donor).To determine if the NPC fraction could play a role in tolerance induction, allogeneic (BALB/c) NPC cells were fluorescently labeled and infused (i.v.) into unreconstituted SCID mice.Two weeks following transplantation, donor-origin NPC cells were found in liver, spleen, thymus, and abdominal lymph nodes, but absent in brain and skeletal muscle.Restoration of immunocompetency in SCID mice transplanted with allogeneic NPC was performed by C3H (syngeneic) bone marrow transplantation and tolerance to donor and recipient antigen demonstrated by full thickness skin grafting with rejection of third-party skin grafts.In conclusion, liver nonparenchymal cells are capable of translocation and residence in lymphoid organs, including the thymus, post-transplantation and may mediate the immuno-protective function of the liver.